The APSY-SED study: protocol of an observational, longitudinal, mixed methods and multicenter study exploring the psychological adjustment of relatives and healthcare providers of patients with cancer with continuous deep sedation until death.

BACKGROUND: Since 2016, France is the only country in the World where continuous deep sedation until death (CDSUD) is regulated by law. CDSUD serves as a response to refractory suffering in palliative situations where the patients' death is expected to occur in the following hours or days. Little is known on the psychological adjustment surrounding a CDSUD procedure for healthcare providers (HCPs) and relatives. Our study aims to gather qualitative and quantitative data on the specific processes behind the psychological adjustment of both relatives and HCPs, after the administration of CDSUD for patients with cancer. METHODS: The APSY-SED study is a prospective, longitudinal, mixed-methods and multicenter study. Recruitment will involve any French-speaking adult cancer patient for who a CDSUD is discussed, their relatives and HCPs. We plan to include 150 patients, 150 relatives, and 50 HCPs. The evaluation criteria of this research are: 1/ Primary criterion: Psychological adjustment of relatives and HCPs 6 and 13 months after the death of the patient with cancer (psychological adjustment = intensity of anxiety, depression and grief reactions, CDSUD-related distress, job satisfaction, Professional Stress and Professional experience). Secondary criteria: a)occurrence of wish for a CDSUD in patients in palliative phase; b)occurrence of wish for hastened death in patients in palliative phase; c)potential predictors of adjustment assessed after the discussion concerning CDSUD as an option and before the setting of the CDSUD; d) Thematic analysis and narrative account of meaning-making process concerning the grief experience. DISCUSSION: The APSY-SED study will be the first to investigate the psychological adjustment of HCPs and relatives in the context of a CDSUD procedure implemented according to French law. Gathering data on the grief process for relatives can help understand bereavement after CDSUD, and participate in the elaboration of specific tailored interventions to support HCPs and relatives. Empirical findings on CDSUD among patients with cancer in France could be compared with existing data in other countries and with results related to other medical fields where CDSUD is also conducted. TRIAL REGISTRATION: This protocol received the National Registration Number: ID-RCB2021-A03042-39 on 14/12/2021.

Focal Neurologic Deficit After Epidural Catheter Removal Leads to Meningioma Diagnosis.

We present an unusual case of a 60-year-old female who developed subtle, new-onset left upper and lower extremity weakness on day five of perioperative thoracic epidural placement. The onset of a focal neurological deficit after epidural placement usually raises suspicion for the presence of an epidural hematoma, abscess, or traumatic cord lesion. However, in this patient, brain imaging revealed a large, previously undiagnosed intracranial mass. Classically, the risk of mass-related intracranial pressure shifts leading to neurological changes is associated with spinal techniques, including diagnostic lumbar puncture, combined spinal-epidural catheter analgesia, and unintended dural puncture during epidural placement. However, based on this case and our summary of case reports in the literature, we determined that symptom onset associated with an intracranial mass may also arise after apparently uncomplicated epidural placement. Symptom onset in our case series ranged from six hours to ten days and was highly variable depending on tumor location, with reported signs and symptoms including headache, vision changes, focal deficits, or alterations of consciousness. Further studies are required to establish definitive causation between the epidural technique and changes in cerebrospinal fluid pressures leading to symptom onset. Though rare, this is a time-sensitive diagnosis that must be considered for any patient with unexplained neurological findings after neuraxial anesthesia.

Induction of broad immunity by thermostabilised vaccines incorporated in dissolvable microneedles using novel fabrication methods.

Dissolvable microneedle (DMN) patches for immunization have multiple benefits, including vaccine stability and ease-of-use. However, conventional DMN fabrication methods have several drawbacks. Here we describe a novel, microfluidic, drop dispensing-based dissolvable microneedle production method that overcomes these issues. Uniquely, heterogeneous arrays, consisting of microneedles of diverse composition, can be easily produced on the same patch. Robustness of the process was demonstrated by incorporating and stabilizing adenovirus and MVA vaccines. Clinically-available trivalent inactivated influenza vaccine (TIV) in DMN patches is fully stable for greater than 6months at 40°C. Immunization using low dose TIV-loaded DMN patches induced significantly higher antibody responses compared to intramuscular-based immunization in mice. TIV-loaded patches also induced a broader, heterosubtypic neutralizing antibody response. By addressing issues that will be faced in large-scale fill-finish DMN fabrication processes and demonstrating superior thermostable characteristics and immunogenicity, this study progresses the translation of this microneedle platform to eventual clinical deployment.

Mechanisms of radiation in a bat group from the genus Pipistrellus inferred by phylogeography, demography and population genetics.

Here, we present a study of the Pipistrellus pipistrellus species complex, a highly diversified bat group with a radiation centre in the Mediterranean biodiversity hotspot. The study sample comprised 583 animals from 118 localities representatively covering the bats' range in the western Palearctic. We used fast-evolving markers (the mitochondrial D-loop sequence and 11 nuclear microsatellites) to describe the phylogeography, demography and population structure of this model taxon and address details of its diversification. The overall pattern within this group includes a mosaic of phylogenetically basal, often morphologically distant, relatively small and mostly allopatric demes in the Mediterranean Basin, as well as two sympatric sibling species in the large continental part of the range. The southern populations exhibit constant size, whereas northern populations show a demographic trend of growth associated with range expansion during the Pleistocene climate oscillations. There is evidence of isolation by distance and female philopatry in P. pipistrellus sensu stricto. Although the northern populations are reproductively isolated, we detected introgression events among several Mediterranean lineages. This pattern implies incomplete establishment of reproductive isolating mechanisms in these populations as well as the existence of a past reinforcement stage in the continental siblings. The occurrence of reticulations in the radiation centre among morphologically and ecologically derived relict demes suggests that adaptive unequal gene exchange within hybridizing populations could play a role in speciation and adaptive radiation within this group.